- Synthesis of N-(2,3,4,5,6-pentafluorobenzyloxy)-γ-lactams by rhodium-catalyzed cyclization of diazo amides
-
Rhodium-catalyzed cyclization of N-(2,3,4,5,6-pentafluoro-benzyloxy) diazo amides leading to the corresponding γ-lactams is described. The cyclization is based on the intramolecular catalytic insertion into the C-H bond. Fourteen lactams were obtained with up to 91 % yield and 88 % ee. Gabapentin hydrochloride, a GABA analog, was also synthesized by this method, which shows that deprotection of the 2,3,4,5,6-pentafluorobenzyloxy group is possible. The rhodium-catalyzed cyclization of diazo amides, derived from O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine, is reported. The reaction leads to a variety of lactams in up to 91 % yield and 88 % ee. The developed method was applied in the synthesis of gabapentin hydrochloride, an important GABA analog.
- Budny, Marcin,Nowak, Magdalena,Wojtczak, Andrzej,Wolan, Andrzej
-
-
Read Online
- Mechanistic investigation on 2-aza-spiro[4,5]decan-3-one formation from 1-(aminomethyl)cyclohexylacetic acid (gabapentin)
-
The intramolecular cyclization of the amino acid gabapentin has been studied in the pH range 2.24-11.15 at 80 °C in buffered solutions and constant ionic strength, and monitoring the progress of the process by fluorimetric method and proton NMR spectrosco
- Zambon, Elena,Giovanetti, Roberto,Cotarca, Livius,Pasquato, Lucia
-
-
Read Online
- Rapid and Mild Lactamization Using Highly Electrophilic Triphosgene in a Microflow Reactor
-
Lactams are cyclic amides that are indispensable as drugs and as drug candidates. Conventional lactamization includes acid-mediated and coupling-agent-mediated approaches that suffer from narrow substrate scope, much waste, and/or high cost. Inexpensive, less-wasteful approaches mediated by highly electrophilic reagents are attractive, but there is an imminent risk of side reactions. Herein, a methods using highly electrophilic triphosgene in a microflow reactor that accomplishes rapid (0.5–10 s), mild, inexpensive, and less-wasteful lactamization are described. Methods A and B, which use N-methylmorpholine and N-methylimidazole, respectively, were developed. Various lactams and a cyclic peptide containing acid- and/or heat-labile functional groups were synthesized in good to high yields without the need for tedious purification. Undesired reactions were successfully suppressed, and the risk of handling triphosgene was minimized by the use of microflow technology.
- Fuse, Shinichiro,Komuro, Keiji,Otake, Yuma,Masui, Hisashi,Nakamura, Hiroyuki
-
supporting information
p. 7525 - 7532
(2021/03/17)
-
- NOVEL PHARMACEUTICAL COMPOSITIONS
-
The present invention relates to a pharmaceutical composition comprising a plurality of layered double hydroxide nanoparticles and one or more pharmaceutically acceptable excipients, wherein the at least one aqueously unstable anionic drug compound is intercalated between the layers. The present invention also relates to a process for the preparation of such pharmaceutical compositions, the corresponding layered double hydroxides, as well as methods for their use in stablising unstable anionic drug compounds.
- -
-
Paragraph 00133-00135
(2017/07/08)
-
- A Simple and Expedient Procedure for the Preparation of Gabapentin Lactam (2-Aza-spiro[4,5]decan-3-one)
-
A novel process has been described on 100 g scale for the preparation of gabapentin lactam which is a penultimate intermediate for the preparation of gabapentin, comprising a Hofmann reaction of 1,1-cyclohexanediacetic acid monoamide using chlorinating agents such as trichloroisocyanuric acid, sodium dichloroisocyanurate, 1,3-dichloro-5,5-dimethylhydantoin, and N-chlorosuccinimide, which have not been employed so far for making this molecule. Reactions done in aqueous alkali on the 1,1-cyclohexanediacetic acid monoamide led to a solution of gabapentin sodium salt which on heating led to the formation of the gabapentin lactam in good yield.
- Katuri, Jashuva V. P.,Ekkundi, Vadiraj S.,Nagarajan, Kuppuswamy
-
p. 1828 - 1832
(2016/10/31)
-
- Chemoenzymatic synthesis of gabapentin by combining nitrilase-mediated hydrolysis with hydrogenation over Raney-nickel
-
An efficient chemoenzymatic process is devised for synthesizing high-purity gabapentin. 1-Cyanocyclohexaneacetic acid was first produced in 0.94 M from 1.0 M 1-cyanocycloalkaneacetonitrile by a greatly improved nitrilase from Acidovorax facilis ZJB09122, resulting in a commercially attractive bioprocess with an outstanding space-time yield of 461 g/L/day. The resulting aqueous 1-cyanocycloalkaneacetic acid was then directly converted to 2-azaspiro [4.5] decan-3-one without further purification in subsequent hydrogenation by Raney-nickel, followed by simple chemical steps to afford gabapentin in high purity and 77.3% overall yield from 1-cyanocyclohexylacetonitrile. The simplicity of the process makes this new pathway suitable for large-scale preparation.
- Xue, Ya-Ping,Wang, Ying-Peng,Xu, Zhe,Liu, Zhi-Qiang,Shu, Xin-Rui,Jia, Dong-Xu,Zheng, Yu-Guo,Shen, Yin-Chu
-
p. 121 - 125
(2015/04/14)
-
- A PROCESS FOR THE PREPARATION OF GABAPENTIN
-
The present invention provides an improved process for the preparation of a compound of formula (I),
- -
-
Page/Page column 24-25
(2014/01/09)
-
- Effect of catalytic alkali metal bromide on Hofmann-type rearrangement of imides
-
The Hofmann-type rearrangement of aromatic and aliphatic imides using KBr as the catalyst proceeded to provide aromatic and aliphatic amino acid derivatives. We have also developed a new synthetic route to gabapentin with this method.
- Moriyama, Katsuhiko,Ishida, Kazuma,Togo, Hideo
-
supporting information; experimental part
p. 8574 - 8576
(2012/09/07)
-
- CRYSTALLINE FORMS OF GABAPENTIN AND PROCESS THEREOF
-
The present invention relates to crystalline forms of gabapentin and processes for preparing the same. The present invention particularly relates to crystalline forms of gabapentin form II and Form IIB. The invention also relates to gabapentin form IA and form IB. The gabapentin forms IA and IB are hydrated forma that contain about 20% of water by weight which corresponds to hemipentahydrate. The present invention also relates to the process for preparing these crystalline forms of gabapentin.
- -
-
Page/Page column 15-16
(2010/04/06)
-
- A Process Suitable for Industrial Scale Production of Gabapentin
-
This invention relates to an improved process for the preparation of substantially pure, stable anhydrous gabapentin. Thus, cyclohexane 1,1-diacetic acid monoamide is first treated with NaOH/NaClO to form 3,3-pentamethylenebutyrolactam, which is treated with aqueous HCl solution under reflux to provide gabapentin HCl salt, which is then neutralized with NaOH followed by a dehydration step to provide substantially pure, storage-stable, pharmaceutical grade gabapentin.
- -
-
Page/Page column 3-4
(2008/06/13)
-
- Process for the preparation of amino methyl cyclo alkane acetic acids
-
This invention relates to an improved process for the preparation of amino methyl cyclo alkane acetic acids. This invention particularly relates to an improved process for the preparation of gabapentin (which is chemically known as 1-aminomethyl-1-cyclohexaneacetic acid), which is a very well known agent useful for the treatment of epilepsy and other cerebral disorders. In the chemical series of 1-amino methyl cyclo alkane-1-acetic acids, Gabapentin, which is 1-amino methyl cyclo hexane-1-acetic acid has been developed as a drug having anti convulsive properties.
- -
-
Page/Page column 7
(2008/06/13)
-
- Process for the preparation of gabapentin
-
A simple, efficient, environmentally improved and economical process for preparing gabapentin, involving enamine alkylation as the key step is disclosed.
- -
-
Page/Page column 4
(2008/06/13)
-
- Dendritic polyglycerol as a high-loading support for parallel multistep synthesis of GABA lactam analogues
-
A general route to 4-substituted azolidin-2-ones (GABA lactam analogues) on a soluble high-loading polyglycerol support has been developed and optimized. These biologically interesting compounds (anticonvulsive drugs) can be synthesized in three steps commencing from a polyglycerol supported (diethylphosphono)acetic acid and a carbonyl compound. The key features of this parallel approach are the cyclative cleavage and simple separation techniques (i.e., dialysis).
- Roller, Sebastian,Siegers, Conrad,Haag, Rainer
-
p. 8711 - 8720
(2007/10/03)
-
- PROCESS FOR THE PREPARATION OF AMINO METHYL CYCLO ALKANE ACETIC ACIDS
-
This invention relates to an improved process for the preparation of amino methyl cyclo alkane acetic acids. This invention particularly relates to an improved process for the preparation of gabapentin (which is chemically known as 1-aminomethyl-1-cyclohexaneacetic acid), which is a very well known agent useful for the treatment of epilepsy and other cerebral disorders. In the chemical series of 1-amino methyl cyclo alkane-1-acetic acids, Gabapentin, which is 1-amino methyl cyclo hexane -1-acetic acid has been developed as a drug having anti convulsive properties.
- -
-
-
- AN IMPROVED PROCESS FOR THE PREPARATION OF GABALACTAM
-
This invention relates an improved process for the preparation of gabalactam. Gablacatam is chemically known as 2-azaspiro(4,5)decan-3-one . Gabalactam has the structural formula 1 given.
- -
-
-
- PROCESS FOR THE PREPARATION OF 1-AMINOMETHYL-1- CYCLOHEXANEACETIC ACID
-
A process for the preparation of gabapentin of formula (I) which comprises: a) reduction of (1-nitromethyl-cyclohexyl)acetonitrile of formula (II) to give 3-imino-2-aza-spiro[4.5]decan-2-ol of formula (III) b) transformation of compound (III), by alkali treatment, into 2-hydroxy-2-aza-spiro[4.5]decan-3-one of formula (IV) c) reduction of compound (IV) to give 2-aza-spiro[4.5]decan-3-one of d) hydrolysis of compound (V) to gabapentin.
- -
-
-
- Hydro-de-halogenation and consecutive deprotection of chlorinated N-amido-pyrrolidin-2-ones with Raney-Ni: An effective approach to gabapentin
-
The benzoylamino group was identified as a useful radical cyclization auxiliary that can be smoothly removed on hydro-de-halogenation of chlorinated N-substituted-pyrrolidin-2-ones with Raney-Ni. This methodology was successfully implemented in a new and appealing route to the anti-epileptic drug gabapentin.
- Cagnoli, Rita,Ghelfi, Franco,Pagnoni, Ugo M.,Parsons, Andrew F.,Schenetti, Luisa
-
p. 9951 - 9960
(2007/10/03)
-
- Metal-catalysed radical cyclisations leading to N-heterocycles: New approaches to gabapentin and pulchellalactam
-
The copper(I) or ruthenium(II)-mediated radical cyclisation of halo-amides has been utilised to afford functionalised pyrrolidinones via 5-endo-trig or 5-exo-trig radical cyclisation pathways. This methodology has been applied to novel and concise syntheses of the anti-epileptic drug gabapentin and the biologically active natural product pulchellalactam.
- Bryans, Justin S.,Chessum, Nicola E.A.,Huther, Nathalie,Parsons, Andrew F.,Ghelfi, Franco
-
p. 6221 - 6231
(2007/10/03)
-
- Process for cyclic amino acid anticonvulsant compounds
-
An improved process for the preparation of cyclic amino acids by a novel synthesis is described where a dinitrile derivative is converted in two steps to the desired products, as well as valuable intermediates used in the process.
- -
-
-
- Process for the preparation of 1-aminomethyl-1-cyclohexaneacetic acid
-
The instant invention concerns a novel process for the preparation of 1-aminomethyl-1-cyclohexaneacetic acid (gabapentin), a known compound useful for treating certain cerebral diseases such as epilepsy and dizziness.
- -
-
-
- Cyclic sulphonyloxyimides
-
The present invention is concerned with new cyclic sulphonyloxyimides and their preparation.
- -
-
-
- Cyclic amino acids
-
The present invention is concerned with new cyclic amino acids and with the preparation thereof.
- -
-
-